Several theories have been presented for the reasons for hair loss including the theory of inferior blood circulation, excessive actions of a male hormone, excessive secretion of sebum, lowering of scalp functions due to dandruff and other bacteria, genetic factors, aging stress, etc. However, nothing has been clarified for the reasons for hair loss until the present time. Moreover, recently, the population suffering from hair loss due to changes in eating habits, increase in stress by social environment, etc. has been on the increasing trend, the ages of such population have been younger, and the female population of hair loss has been increased.
Among the above reasons for hair loss, the most frequently seen type of hair loss which is directly related to the excessive secretion of a male hormone is androgenic alopecia, called male pattern baldness usually. A male having androgenic alopecia shows phenomena that his healthy hairs become thinner, shorter, and weaker gradually, and readily broken. These phenomena are called miniaturization, during which hair follicles become thinner, unnoticeable, and changed to short downy hair eventually leading to hair loss. Accordingly, recently, many studies on the prevention and treatment of hair loss through the suppression of activities of a male hormone have been reported.
Male pattern baldness, which is the most frequently seen type of hair loss, is induced as testosterone, one of male hormones, is converted into dihydrotestosterone (DHT), which is an active-type male hormone, by 5α-reductase, and thus activated dihydrotestosterone is combined with an androgen receptor making the synthesis of proteins of follicular cells delayed, the growing period of follicles shortened, and follicles shrunk. Also, sebum may be produced excessively during the process of androgenic alopecia, and as a result, hair loss accompanied by inflammation may be shown on the scalp [Dennis A Holt et al., J. Med. Chem., 33, 943 (1990)].
In the meantime, it has been known that there have been more various reasons for female hair loss compared with those for male hair loss. But in reality, androgenic alopecia generated as the sensitivity to the male hormone is inherited occupies about 50% of hair loss of adult females.
The mechanism of male pattern baldness coming from the excessive production of dihydrotestosterone by the actions of 5α-reductase suggests that it is possible to prevent and treat effectively androgenic alopecia by using anti-androgenic activation effects suppressing the activities of 5α-reductase or the combination with an androgenic receptor, or by using the actions of estrogen conversion acceleration of androgen.
The treatment drug proposed based on the above theoretical basis is Propecia (of which main component is finasteride) manufactured and sold by Merck & Co., Inc. of the U.S.A. Finasteride shows a mechanism of suppressing the conversion of testosterone, which is a male hormone, to dihydrotestosterone, which is a strong active-type male hormone. It has been the only oral treatment drug on the market of the world since it was approved by FDA of the U.S. as a treatment agent of active-type hair loss in 1997 (U.S. Pat. Nos. 4,377,584 and 4,760,071, Korean Patent No. 10-0415858, Korean Laid-Open Patent No. 2003-0042504). And yet, Propecia is disadvantageous in that its effects are shown several months after it is administered, there are side effects such as diminution of sexuality, impotence, etc., it may be used only for males, and safety for being used for females and children is not established presently, and its use for pregnant women or fertile women is strictly prohibited.
Further, the most widely used formulation for the treatment or prevention of hair loss is Minoxidil (6-(1-piperidinyl-2,4-pyrimidineamine-3-oxide) (U.S. Pat. No. 4,139,619) developed by Pharmacia Sverige AB and approved by FDA of the U.S. as a drug accelerating re-growth of hair. Minoxidil has been a vasodilation (K+) channel opener for the treatment of high blood pressure acting as a smooth muscle vasodilator, but became more famous as an epilation drug as an epilation phenomenon has been shown as a side effect in using it. This drug has been somewhat effective (20 ?30%) when it has been applied externally to young people or people having oily hair or people having the whirl of hair on the head fallen out, but in other cases, not only it has shown insignificant effects but also there have been reported some side effects such as contact dermatitis, dried mouth, lowering of blood pressure, dizziness, etc., but also it has been troublesome to use it since it has had to be used a few times every day. Besides the above, hair tonics containing hyperosmotic extracts, hair-growing agents, epilation prevention agents containing hyperosmotic extracts, and the mechanism of the actions of 5α-reductase have been disclosed (Japanese Laid-Open Patents Nos. PYUNG7-267830, PYUNG7-277930, and PYUNG5-58851, Korean Patent No. 10-0311199).
Still further, among diseases induced due to an excessive amount of dihydrotestosterone, particularly, benign prostatic hyperplasia (BPH) is shown in proportion to the ages of males who are older than 50 years old and brings about pain coming from dysuria due to pressing of urinary tract. Causal treatment of this disease is available through the ectomy of enlarged prostatic tissues. However, since most of patients has been aged making the objects of operation limited and there have been problems of side effects, recurrence, etc. after operation, expectation for simple drug therapies has been increased.
5α-reductase inhibitor has been recognized as a safe and causal treatment agent of benign prostatic hyperplasia since it has been possible to treat urination impairment by reducing enlarged prostate gland without any side effects found in anti-male-hormone drugs by showing the anti-androgenic activity effects by selectively suppressing the production of dihydrotestosterone without affecting testosterone showing the actions of a male hormone. Therefore, the compounds such as finasteride (product name is Proscar manufactured and sold by Merck Pharmaceutical Company) suppressing the production of dihydrotestosterone in tissues by hindering the actions of this 5α-reductase is on the market and used currently as a treatment agent of benign prostatic hyperplasia (U.S. Pat. Nos. 4,377,584 and 4,760,071, Korean Laid-Open Patents Nos. 2003-22763, 2000-0075651, and 2004-0016559).
In the meantime, a pharmaceutical composition of which effective component is 2-[2-[4-[(4-chlorophenyl)phenylmethyl]-1-piperazinyl]ethoxy]-acetic acid (chemical formula is C21H25ClN2O3, molecular weight is 388) of the present invention and its pharmaceutically acceptable salt has been on the market as an anti-allergic agent, anti-histamine agent, bronchodilator, and spasmolytic and known to be an FDA-approved product having no side effects and superior safety. However, nothing has been reported up to the present time as to where it might have been used as a useful active component for the prevention of baldness and fall-out of hairs, epilation, hair toning, hair growth, and the treatment of female hirsutism, benign prostatic hyperplasia, or the like, which are the objects of the present invention.